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Corticosteroid-potentiated vascular responses of the equine digit: a possible pharmacologic basis for laminitis.

Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invariably underwent an additional contraction. In venous and arterial strips, dose-response curves to epinephrine, norepinephrine, serotonin, or histamine were established in the absence and in the presence of corticosteroid. Effects of the amines, except histamine, were markedly potentiated. The degree of corticosteroid/amine potentiation was greater for epinephrine than for norepinephrine and greater in the digital vein than in the corresponding artery from the same animal. Betamethasone was more potent than hydrocortisone.

Adrenal Cortex Hormones↗

The power athlete.

A number of normal daily and athletic activities require isometric or static exercise. Sports such as weight lifting and other high-resistance activities are used by power athletes to gain strength and skeletal muscle bulk. Static exercise, the predominant activity used in power training, significantly increases blood pressure, heart rate, myocardial contractility, and cardiac output. These changes occur in response to central neural irradiation, called central command, as well as a reflex originating from statically contracting muscle. Studies have demonstrated that blood pressure appears to be the regulated variable, presumably because the increased pressure provides blood flow into muscles whose arterial inflow is reduced as a result of increases in intramuscular pressure created by contraction. Thus, static exercise is characterized by a pressure load on the heart and can be differentiated from the hemodynamic response to dynamic (isotonic) exercise, which involves a volume load to the heart. Physical training with static exercise (i.e., power training) leads to concentric cardiac (particularly left ventricular) hypertrophy, whereas training with dynamic exercise leads to eccentric hypertrophy. The magnitude of cardiac hypertrophy is much less in athletes training with static than dynamic exercise. Neither systolic nor diastolic function is altered by the hypertrophic process associated with static exercise training. Many of the energy requirements for static exercise, particularly during more severe levels of exercise, are met by anaerobic glycolysis because the contracting muscle becomes comes deprived of blood flow. Power athletes, training with repetitive static exercise, derive little benefit from an increase in oxygen transport capacity, so that maximal oxygen consumption is increased only minimally or not at all. Peripheral cardiovascular adaptations also can occur in response to training with static exercise. Although the studies are controversial, these adaptations include modest decreases in resting blood pressure, reduced increases in blood pressure and sympathetic nerve activity during a given workload, enhanced baroreflex function, increases in muscle capillary-to-fiber ratio, possible improvements in lipid and lipoprotein profiles, and increases in glucose and insulin responsiveness. Some of these adaptations can occur in cardiac or hypertensive patients with no concomitant cardiovascular complications. In both healthy individuals and those with cardiovascular disease, the manner in which resistance training is performed may dictate the extent to which these adjustments take place. Specifically, training that involves frequent repetitions of moderate weight (and hence contains dynamic components) seems to produce the most beneficial results.

Adaptation, Physiological↗

Double sucrose-gap method applied to single muscle fiber of Xenopus laevis.

Passive electrical properties (internal conductance, membrane conductance, low frequency capacity, and high frequency capacity obtained from the foot of the action potential) of normal and glycerol-treated muscle of Xenopus were determined with the intracellular microelectrode technique. The results show that the electrical properties of Xenopus muscle are essentially the same as those of frog muscle. Characteristics of the action potential of Xenopus muscle were also similar to those of frog muscle. Twitch tension of glycerol-treated muscle fibers of Xenopus recovered partially when left in normal Ringer for a long time (more than 6 h). Along with the twitch recovery, the membrane capacity increased. Single isolated muscle fibers of Xenopus were subjected to the double sucrose-gap technique. Action potentials under the sucrose gap were not very different from those obtained with the intracellular electrode, except for the sucrose-gap hyperpolarization and a slight tendency toward prolongation of the shape of action potential. Twitch contraction of the artificial node was recorded as a change of force from one end of the fiber under the sucrose gap. From the time-course of the recorded force and the sinusoidal stress-strain relationship at varying frequencies of the resting muscle fiber, the time-course of isotonic shortening of the node was recovered by using Fourier analysis. It was revealed that the recorded twitch force can approximately be regarded as isotonic shortening of the node.

Action Potentials↗

Effect of endotoxin on canine colonic motility and transit.

Diarrhea is a common problem in patients who have episodes of sepsis and are being fed enterally. Endotoxemia results in gastrointestinal motor dysfunction characterized by slowed gastric emptying and rapid intestinal transit; however, the effect of endotoxin on colonic motility is unknown. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on colonic motility and transit. Seven dogs underwent construction of a 50 cm colonic Thiry-Vella fistula. Five manometry catheters were sewn into the colonic lumen at 8 cm intervals along the fistula. Following recovery, the fistula was perfused with an isotonic solution at 2.9 ml/min, and fasting and postprandial colonic motility was determined. Liquid transit was assessed by bolus of a nonabsorbable marker instilled into the proximal end of the Thiry-Vella fistula. Recordings of gastrointestinal contractile activity were made digitally to determine contractile frequencies and motility indexes. Following completion of the baseline studies, each dog was given a single dose of E. coli lipopolysaccharide, 200 microgram/kg intravenously, and studies were repeated daily for the next 3 days. Endotoxin doubled the fasting colonic contractile frequency on postendotoxin day 1 and also increased motility indexes on that same day. Fasting motility indexes and contractile activity were decreased on postendotoxin days 2 and 3. The postprandial frequency of contractions and motility indexes were decreased on postendotoxin day 3. Fasting colonic liquid transit was rapid on postendotoxin day 1, whereas postprandial liquid transit was rapid on both postendotoxin days 1 and 2. Endotoxin temporarily speeds liquid transit and increases both the frequency and strength of colonic contractions. These effects may contribute to the diarrhea that occurs during episodes of sepsis.

Animals↗

Rigor contraction and the effect of various phosphate compounds on glycerinated insect flight and vertebrate muscle.

1. Glycerol-extracted flight muscle from the giant water-bug, Lethocerus cordofanus, undergoes contraction when deprived of ATP. This rigor contraction occurs in the presence of the calcium chelating agent EGTA, under conditions in which the predicted free calcium ion concentration is less than 5 x 10(-9)M. A mechanically similar contraction has been observed by depriving the muscle of Mg(2+), in the presence of 5 mM-ATP.2. In the rigor contraction tensions of up to 120 mN/mm(2) under isometric conditions, and shortenings of between 2(1/2) and 6% under isotonic conditions, have been observed at 20 degrees C.3. Muscles in rigor can be relaxed by the addition of ATP. The minimum concentration of ATP required to give full relaxation depends upon other ionic constituents of the solutions, and upon temperature, but is between 0.3 and 1 mM at 20 degrees C. Lower concentrations result in partial reduction of tension and stiffness.4. Pyrophosphate (PP) causes a reduction in the tension of muscle which has developed rigor under isometric conditions, but the stiffness, when measured at frequencies between 1 and 100 Hz, remains indistinguishable from that of rigor muscle. The stiffness when measured by applying slow length changes is comparable to that of ATP-relaxed muscle. It is suggested that in PP-relaxed muscle the cross-bridges remain in close proximity to, but are not rigidly attached to, the I filaments, resulting in a high viscous interaction between the two sets of filaments.5. The addition of low concentrations of ADP (less than about 0.7 mM) to rigor muscle in the absence of ATP causes an increase in tension. The effect is sigmoid, and is probably due to the formation of low concentrations of ATP throughout the body of the fibre by myokinase activity. Larger concentrations of ADP (about 5 mM) added to rigor muscle cause relaxation, probably due to the formation of higher ATP concentrations.6. AMP and inorganic orthophosphate have little effect upon the mechanical properties of rigor muscle.7. There is a delay of about 1 min before the onset of rigor contraction when fibres are transferred from an ATP-solution to one containing no ATP, due to the transfer of ATP in the body of the fibres. Both ATP hydrolysis by the fibres and diffusion of ATP into the bathing solution contribute significantly to the rate of depletion of ATP.8. Rabbit psoas muscle shows a similar rigor contraction in the presence of EGTA, and has mechanical properties similar to those described for Lethocerus flight muscle in the presence of pyrophosphate.

Adenine Nucleotides↗

Hydrostatic pressure in epidermal cells is dependent on Ca-mediated contractions.

Volume/osmotic pressure relationships were compared in Xenopus epidermal cells treated with the calcium antagonist lanthanum and in control cells. In lanthanum-treated cells the volume was found to be proportional to the reciprocal of the osmotic pressure in the hypotonic range, but not in the control cells. This difference is interpreted as being caused by contractions of the actomyosin system in control cells, which require external calcium. On the basis of the different slopes of the measurements under these two conditions the contractile force of the cells in isotonic conditions was calculated to be 0.96 x 10(5)Nm-2. The observation that in hypotonic media the cell body is enlarged in the direction of movement provides evidence that the cell body/lamella transition region is the part of the cell that contracts most during locomotion. By analysing cell speed in media with varying osmotic pressures, the relationship between internal pressure and cell locomotion was revealed.

Animals↗

Alfentanil attenuates phenylephrine-induced contraction in rat aorta.

BACKGROUND AND OBJECTIVES: Alfentanil was reported to relax the rat aorta by direct action on the vascular smooth muscle. The aims of this in vitro study were to examine the effect of alfentanil on phenylephrine-induced contractions in the rat aorta and to determine the cellular mechanism associated with this process. METHODS: Endothelium-denuded aortic rings were suspended in order to record isometric tension. In the rings with or without 10(-6) mol naloxone or 10(-5) mol verapamil, the concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of alfentanil (10(-6), 5 x 10(-5), 10(-4) mol). In the rings exposed to a calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence or absence of alfentanil (5 x 10(-5), 10(-4) mol). RESULTS: Alfentanil (5 x 10(-5), 10(-4) mol) attenuated (P < 0.05) the phenylephrine-induced contraction in the ring with or without 10(-6) mol naloxone but had no effect on the phenylephrine-induced contraction in the rings pretreated with verapamil. Alfentanil (5 x 10(-5), 10(-4) mol) produced a significant rightward shift (P < 0.01) in the potassium chloride dose-response curve, and attenuated the contractile response (P < 0.001) induced by calcium in the calcium-free isotonic depolarizing solution in a dose-dependent manner. CONCLUSIONS: A supraclinical dose of alfentanil attenuates the phenylephrine-induced contraction via an inhibitory effect on calcium influx by blocking the l-type calcium channels in the rat aortic vascular smooth muscle.

Alfentanil↗

Differences in activation patterns in elbow flexor muscles during isometric, concentric and eccentric contractions.

To investigate the relative activation of the synergistic muscles during three different types of muscle contraction, the electromyograms (EMG) of two elbow flexor muscles, the biceps brachii (BB) and the brachioradialis (BR), have been compared. To accomplish this eight healthy human subjects performed the following elbow flexions against the same load--concentric, eccentric and isometric contractions. The isometric contractions were performed at three elbow angles: 10, 45 and 90 degrees (0 degree equal to full extension). The EMG were recorded by bipolar surface electrodes, and the relative activation between the two muscles was evaluated as the quotient of mean EMG activities (BR/BB). For the isotonic elbow flexions, BR/BB were calculated at three angle divisions: 0-30 degrees, 30-60 degrees and 60-90 degrees. Results indicated that the relative activation of the BR during the concentric contractions was higher than that of the eccentric contraction, particularly at the extended elbow angles, i.e. the BR/BB of the concentric contractions for the elbow joint angles ranging from 0-30 degrees and 30-60 degrees were significantly greater (P < 0.05) than those of the eccentric contractions. During the isometric and eccentric contractions, the BR/BB at the flexed joint angles tended to be greater than those at the extended angles. In contrast, there were no angle-dependent BR/BB variations during the concentric elbow flexions. Further, changing patterns in the EMG power spectra due to the type of contraction were different between BB and BR. These results indicated that the activation pattern in the two elbow flexor muscles varied with the muscle contraction pattern.

Adult↗

Preload does not affect relaxation rate in normal, hypoxic, or hypertrophic myocardium.

To determine whether isolated changes in preload (end-diastolic force) can influence myocardial relaxation rate in normal or abnormal (hypoxic or hypertrophic) hearts, isolated LV papillary muscles from normal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were studied using physiologically sequenced contractions. While total (systolic) load and late (lengthening) load were held constant, maximum isometric force decline (peak -dT/dt) and maximum isotonic lengthening rate (peak +dL/dt) were measured at seven levels of preload that varied from 115 to 55% of the resting tension at maximum length-tension curves (Lmax). Muscles from normal rats were studied in the oxygenated state (95% O2-5% CO2) and in the hypoxic state (95% N2-5% CO2). Preload did not effect peak -dT/dt or peak +dL/dt in either oxygenated or hypoxic muscles. During hypoxia, peak -dT/dt and peak +dL/dt were 9.5 +/- 1.0 g.mm-2.s-1 and 0.3 +/- 0.1 muscle length/s, respectively, at a preload of 115% compared with 9.0 +/- 1.2 g.mm-2.s-1 and 0.2 +/- 0.1 at a preload of 55%. In separate experiments, the effect of preload on relaxation rate was studied in WKY and SHR rats. In neither group did preload have an independent effect on relaxation rate. In the SHRs, peak -dT/dt and peak +dL/dt were 24.3 +/- 5.3 g.mm-2.s-1 and 0.7 +/- 0.1 muscle length/s, respectively, at a preload of 115% compared with 24.7 +/- 6.6 and 0.8 +/- 0.1 at a preload of 55%. Thus, in hypoxic and hypertrophic myocardium, as in normal muscle, an acute isolated change in preload did not influence the rate of force decline or muscle lengthening.

Animals↗

Comparison of cerebellar intention tremor under isotonic and isometric conditions.

The characteristics of cerebellar intention tremor were investigated by comparing the properties of tremor following movements about the elbow with that following isometric contractions of biceps and triceps brachii. Cerebellar dysfunction was produced by local, reversible cooling of the dentate and interposed nuclei in three Cebus monkeys. Cerebellar nuclear cooling disrupted isometric contractions to the aimed target and produced oscillations in torque. Whereas the cerebellar tremor that followed movements was regular and had a frequency of 3-5 Hz, the oscillations in the isometric task were irregular and were often of a lower frequency. In addition, cycles of tremor following movements were in phase from trial to trial, while the oscillations that occurred following isometric contractions did not show this phase-relationship. It is concluded that a cerebellar tremor can occur in an isometric situation but that movement about a joint is required for development of a rhythmic 3-5-Hz cerebellar intention tremor.

Animals↗

Effects of experimental muscle pain on mechanical properties of single motor units in human masseter.

OBJECTIVE: Muscle pain is known to influence muscle activity but the details of its effects on the mechanical properties of single motor units (SMU) have not been described. We have recently reported a decreased firing rate of SMU in the human masseter muscle during painful contractions with a constant force output. Force output can be modulated by the SMU discharge rate in relation to the contractile properties of SMU. Therefore, the objective of the present study was to measure the mechanical properties of SMU in the masseter to clarify the mechanism which underlies the decrease in SMU firing rate during jaw-muscle pain. METHODS: A spike-triggered averaging (STA) technique was used to determine the mechanical properties of low-threshold SMU in the masseter muscle recorded with fine wire electrodes during a voluntary isometric contraction. The twitch amplitude, contraction time, and half-relaxation time were determined from the averaged force records before and during experimental jaw-muscle pain induced by injection of 0.2 ml (100 microg/ml) capsaicin in 8 healthy subjects. Injections of 0.2 ml isotonic saline served as a non-painful control in 11 healthy subjects. RESULTS: The twitch amplitude was significantly increased during capsaicin-evoked muscle pain (P<0.001) without significant changes of half-relaxation time and contraction time. No significant changes in SMU twitch properties were observed during the control injections. CONCLUSIONS: Potentiation of twitch force could be a possible compensatory mechanism to maintain a constant force output during painful isometric contractions when SMU firing decreases. This finding therefore provides new information on the adaptation of motor function by muscle pain.

Adult↗

The effect of duodenal infusion on the electromyogram of gastric muscle during activation and inhibition of gastric emptying.

1. When the abomasum of the conscious calf is partially distended, rhythmic motility can readily be recorded from the e.m.g. of the smooth muscle of the fundus (body) and antrum. 2. In gastric evacuation rhythmic contractions of the antrum are reinforced by both rhythmic and tonic fundic contractions. 3. The output volume of the stomach can be directly correlated with e.m.g. activity. 4. Intragastric fluid is usually emptied in gushes coinciding with a strong contraction of the antrum but fluid may be evacuated, when the antrum is inactive, through the force generated by persisting rhythmic fundic contractions. 5. Using re-entrant cannulae so that the duodenum can be infused separately from the gastric effluent, isotonic sodium bicarbonate produced almost 100% gastric evacuation with greatly enhanced e.m.g. activity of fundus and antrum. Infusion of the duodenum with a solution of HCl, 60 m-equiv/l., produced the opposite effect, the gastric muscle becoming quiescent and 100% of the gastric test meal being retained. 6. These results show that the activating or inhibitory effects of a duodenal infusate are produced through an activating or inhibitory effect on the smooth muscle of the stomach. 7. The mechanism of the interrelation between duodenal receptor and gastric effector has not yet been elucidated but the connexion is not intramural since it continues when the duodenum is transected near to the pylorus.

Abomasum↗

Effects of variations in extracellular osmolality on spontaneous contractile activity and response to nerve stimulation in rat detrusor muscle in vitro.

The effects of hyperosmolar (390, 590 mosm/kg) and hypoosmolar (260 mosm/kg) solutions on myogenic spontaneous contractile activity and response to nerve stimulation were studied on strips of rat detrusor muscle in vitro. In isotonic (290 mosm/kg) solution the mean spontaneous contractile activity was 2.1 +/- 0.6% and the amplitude of the largest spontaneous contractions was 9.8 +/- 3.0% of maximal response to nerve stimulation. In 390 mosm/kg the frequency of spontaneous contractions decreased, but due to a fourfold increase of contraction amplitude a threefold increase of mean contractile activity was recorded. In 260 mosm/kg a similar contraction pattern as in 290 mosm/kg was seen. The spontaneous contractions were resistant to tetrodotoxin (10(-5) g/ml) in all osmolalities. In 590 mosm/kg the spontaneous activity had ceased, and a continuous contracture (resistant to tetrodotoxin) was observed with an amplitude of 41 +/- 1% of the maximal response to nerve stimulation at 290 mosm/kg. Similar maximal responses to nerve stimulation were obtained in 260, 290, and 390 mosm/kg. The frequency-response relation in 390 mosm/kg had a leftward shift at low frequencies. In 590 mosm/kg no response to nerve stimulation or acetylcholine was noted, but the preparations contracted vigorously following depolarization with high-K+ solution.

Animals↗